Circulating tumor cells: clinical validity and utility

Abstract

Circulating tumor cells (CTCs) are rare tumor cells and have been investigated as diagnostic, prognostic and predictive biomarkers in many types of cancer. Although CTCs are not currently used in clinical practice, CTC studies have accumulated a high level of clinical validity, especially in breast, lung, prostate and colorectal cancers. In this review, we present an overview of the current clinical validity of CTCs in metastatic and non-metastatic disease, and the main concepts and studies investigating the clinical utility of CTCs. In particular, this review will focus on breast, lung, colorectal and prostate cancer. Three major topics concerning the clinical utility of CTC are discussed-(1) treatment based on CTCs used as liquid biopsy, (2) treatment based on CTC count or CTC variations, and (3) treatment based on CTC biomarker expression. A summary of published or ongoing phase II and III trials is also presented.

Role of Circulating Tumor Cells and Cell-Free Tumor Deoxyribonucleic Acid Fragments as Liquid Biopsy Materials in Breast Oncology

“…At the first step, CTCs are selected in LB samples either by positive selection (enrichment) or negative selection (depletion) methods. [10] Immunomagnetic-/microfluidic-based Table 1 The advantages of liquid biopsy collection over standard biopsy not alternatives because these methods have less specificity compared to the other methods. Thus utilization of mRNA expression detection methods have been discontinued as part of the detection systems, but studies are ongoing.…”

“…Epithelial cell adhesion molecule (EpCAM) is the most frequently used biomarker targeted by immunomagnetic enrichment methods. [10] ISET (isolation by size of epithelial tumor cells) filtration of CTCs method is used based on the fact that CTCs are slightly bigger than red and white blood cells. [11] Cells, other than CTCs in the blood are cross-linked to erythrocytes and removed for negative selection with density gradient centrifugation.…”

“…[11] CellSearch system is currently the gold standard method for breast CTC detection by being the only Food and Drug Administration (FDA)-approved method. [10,11] This system targets EpCAM molecule on cell surface of CTCs for positive selection at the first step of CTC detection. EpCAM-positive CTCs are isolated from blood by immunomagnetic selection and then fluorescently labeled for DAPI, CD45 and CK19 to be sure about breast CTCs at the second step of the system.…”

“…EpCAM-positive CTCs are isolated from blood by immunomagnetic selection and then fluorescently labeled for DAPI, CD45 and CK19 to be sure about breast CTCs at the second step of the system. [10,11] Currently, CTCs isolated with CellSearch system are in utilization for prognosis evaluation of BC patients. Downstream high-throughput genomic, transcriptomic or proteomic characterization methods can also be used as alternatives of validation step of the system.…”

“…Downstream high-throughput genomic, transcriptomic or proteomic characterization methods can also be used as alternatives of validation step of the system. [10,11] However, mRNA expression detection based RT-PCR or probe-based methods are currently of cancer patients is called 'liquid biopsy' (LB). [7] Recently, LB is becoming hotspot research topic mainly due to its remarkable advantages in comparison to tissue biopsy (Table 1).…”